P. Noize

Engagement in leisure activities and benzodiazepine use in a French community-dwelling elderly population

The prevalence of benzodiazepine use among community‐dwelling older persons varies between 10% and 30%. The aim of this study was to explore the association between leisure activities and the use of benzodiazepine among older persons living at home.

Prevalence and prescription patterns of oral glucocorticoids in adults: a retrospective cross-sectional and cohort analysis in France

Objectives To study trends in use of oral glucocorticoids (GCs) among adults, characteristics of oral GC initiators and prescriptions for the prevention of potential adverse effects associated with GC therapy. Design First, a cross-sectional study repeated yearly was performed from 2007 to 2014 in a nationwide representative sample. Second, characteristics of initiators and patterns of GC therapy during the year following treatment initiation were described in a cohort of patients who began GC between 2007 and 2013. Setting Population-based study using data from the French reimbursement healthcare system (covering approximately 90% of the population) in patients aged ≥18 years. Results Over the study period, the prevalence of oral GC use ranged from 14.7% to 17.1% (95% CI 17.0%–17.2%) with a significant increase of 14.1% (95% CI +13.5% to +14.8%). The 2007–2013 cohort of oral GC initiators comprised 206 759 individuals. Oral GC use was mostly short-term (68% of unique reimbursement) and more than half of short-term users took concurrent antibiotics or respiratory/otological drugs. Chronic users (≥6 reimbursements/year) represented 1.8% (n=3789) of the cohort. The proportion of chronic users with comorbidities likely to be worsened by GC use (diabetes, psychotic disorders, osteoporosis) was 25%. Among patients at increased risk of osteoporosis, 62% received specific prevention/monitoring measures and only 27% had a bisphosphonate. Half of chronic oral GC users had a concurrent reimbursement of a proton pump inhibitor in the absence of non-steroidal anti-inflammatory drug use. Conclusions Oral GC use was highly widespread and increased among adults from 2007 to 2014. The overwhelming short-term use could mainly concern a growing use of unjustified prescriptions rather than situations with a favourable benefit/risk ratio. For chronic users, our findings plead for the development of interventions designed to improve monitoring with regard to the frequent comorbidities at risk and inappropriate prescribing of preventive therapeutic measures.

Use of Lipid‐Lowering Drugs and the Risk of Cataract: A Population‐Based Nested Case‐Control Study

Eye lens membrane cells require high cholesterol concentrations that might be counteracted by lipid‐lowering drugs. Using a nationwide database, we conducted a nested case‐control study to evaluate the risk of cataract development associated with the use of lipid‐lowering drugs. Patients aged 45 years and over with first cataract surgery in 2014 (cases) and up to four controls matched on age, gender, diabetes, hypothyroidism, glucocorticoid use, cardiovascular risk, and area of residence were included in the study. Among the 2,811 cases and 11,106 matched controls included, analyses showed a significantly increased risk of cataract surgery for a cumulative exposure to fibrates exceeding 5 years (adjusted odds ratio (aOR) 1.58; 95% confidence interval (CI): 1.17–2.15), unlike cumulative exposure to statins, whatever the dose or duration of treatment (aORs from 1.00–1.08, none being significant). This study highlighted an increased risk of cataract surgery with prolonged use of fibrates but not of statins.

Effectiveness of Cetuximab as First-Line Therapy for Patients With Wild-Type KRAS and Unresectable Metastatic Colorectal Cancer in Real-Life Practice: Results of the EREBUS Cohort

Introduction Few real‐life data are available on cetuximab benefit. The EREBUS cohort was performed to assess metastases resection rate, use, safety, and survival outcomes in wild‐type KRAS (Kirsten rat sarcoma viral oncogene) patients with initially unresectable metastatic colorectal cancer (mCRC) treated by cetuximab in real practice. Patients and Methods The study cohort comprised patients initiating cetuximab between January 2009 and December 2010 in 65 French centers, with initially unresectable mCRC and wild‐type KRAS. Kaplan‐Meier analysis estimated 24‐month probability of metastases resection and progression‐free survival, and 36‐month overall survival (OS). Cox proportional hazards models investigated factors associated with survival outcomes. Results Among the 389 patients included, median age was 64 years, 67.4% were male, 77.9% had Eastern Cooperative Oncology Group performance status ≤ 1, and hepatic metastases were most frequent at baseline (n = 146 exclusively, n = 149 not exclusively, n = 94 nonliver only). Median duration of cetuximab use was 4.8 months. Metastases resection was performed in 106 patients (27.2%) (n = 60 liver exclusively, n = 33 not exclusively, n = 13 nonliver only). The 24‐month probability (95% confidence interval) of metastases resection occurrence was 33.6% (28.5‐39.3). Median progression‐free survival was 9.2 (8.5‐9.8) months for the total cohort and 13.0 (11.6‐15.1) for those resected; median OS was 23.0 (20.6‐26.3) months for the total cohort and was not reached after 36 months for those who were resected. The strongest factor associated with higher OS was metastases resection with complete remission (hazard ratio, 0.41; 95% confidence interval, 0.19‐0.88). Conclusion This cohort study highlights in French real‐life practice the benefit of cetuximab in first‐line mCRC therapy, notably in case of metastases resection with complete remission. Micro‐Abstract Cetuximab has demonstrated to improve survival outcomes in metastatic colorectal cancer (mCRC), but real‐life information is sparse. In the EREBUS cohort, effectiveness and safety were assessed in wild‐type KRAS mCRC patients with initially unresectable metastases and treated by cetuximab as first‐line therapy. Secondary metastases resection was observed in 27% of patients after first‐line cetuximab with chemotherapy, with significant benefit after complete remission.

Development and validation of hospital information system-generated indicators of the appropriateness of oral anticoagulant prescriptions in hospitalised adults: the PACHA study protocol

Introduction The appropriateness of oral anticoagulant prescriptions is a major challenge to improve quality and safety of care. As indicators of the appropriateness of oral anticoagulant prescriptions are lacking, the aim of the study is to develop and validate a panel of such indicators, in hospitalised adults, from the hospital information system of two university hospitals in France. Methods and analysis The study will be carried out in four steps: (1) a literature review to identify indicators of the appropriateness of oral anticoagulant prescriptions and their conditions of appropriateness; (2) a Delphi consensus method to assess the potential utility and operational implementation of the selected indicators; (3) techniques of medical data search to implement indicators from the hospital information system and; (4) a cross-sectional study to assess the ability of indicators to detect inappropriate oral anticoagulant prescriptions, performance of medical data search techniques for tracking or retrieving information and the ability of tools to be transferred into other institutions. The fourth step will include up to 80 patient hospital stays for each indicator, depending on the prevalence of inappropriate prescriptions estimated in interim analyses. Ethics and dissemination This work addresses the current lack of quality indicators of the appropriateness of oral anticoagulant prescriptions. We aim to develop and validate such indicators for integrating them into hospital clinical practice, as part of a structured approach to improve quality and safety of care. As each hospital information system is different, we will propose tools transferable to other healthcare institutions to allow an automated construction of these indicators. The PACHA study protocol was approved by institutional review boards and ethics committees (CPP Sud-Ouest et Outre Mer III—DC 2016/119; CPP Ile-de-France II—CDW_2016_0014). Registration details Clinical Trial.gov registration: NCT02898090.

Definition of indicators of the appropriateness of oral anticoagulant prescriptions in hospitalized adults: Literature review and consensus (PACHA study)

BACKGROUND Indicators of the appropriateness of oral anticoagulant prescriptions are lacking, despite the major contribution they could make to improve quality of care. AIM To identify and select such indicators according to their utility and operational implementation. METHODS A literature review was conducted to identify indicators of the appropriateness of oral anticoagulant prescriptions according to the guidelines of health authorities and European learned societies. A first list of indicators was identified from guidelines related to general or targeted clinical situations. A two-round Delphi consensus process, completed by a synthesis meeting, was then set up to ask European experts to rate the utility and operational implementation of the indicators on a qualitative binary scale. An indicator was selected if ≥80% of the experts judged it both useful and implementable (strong consensus). RESULTS We selected 32 references, from which 84 indicators were identified. Nineteen indicators were short-listed for submission to expert judgment. Twenty-two experts participated in the Delphi process. Sixteen indicators obtained strong consensus for selection; three indicators did not achieve consensus. Two-thirds of the selected indicators focused on the appropriateness of oral anticoagulant prescriptions in general or in patients with atrial fibrillation; the other third focused on the appropriateness of prescriptions in patients with a prosthetic heart valve, venous thromboembolism or trauma. CONCLUSION This work addresses the current lack of indicators of the appropriateness of oral anticoagulant prescriptions. The selected indicators will be implemented from the hospital information system to assess their metrological properties to detect inappropriate prescriptions.

Cetuximab in first-line treatment of metastatic colorectal cancer in a real-life setting: Preliminary results of the EREBUS cohort.

621 Background: Cetuximab (CTX) has demonstrated to improve survival outcomes in metastatic colorectal cancer (mCRC), but little data for real-life use is available. METHODS EREBUS is a French multicentre (n=92) hospital-based cohort. Patients initiating CTX in 2009 and 2010 were identified retrospectively from registries of nominative drug dispensations. Those with wild-type KRAS gene receiving 1st-line treatment for mCRC were followed-up for 12 months. Data were collected from patient medical records and response based on physician assessments (CT-Scan). Presented here are preliminary results of the EREBUS cohort about administration regimen and according response rates for patients included in 2009. RESULTS Of the 190 patients included in the cohort, data has been collected for 160 (84.2%): median age at baseline 65.5 years, 70.6% male. Regarding cancer characteristics, 79.4% of patients had a colon cancer and 53.8% a primary tumor resection. Metastatic sites were liver in 73.1% of patients, peritoneum in 29.4%, lymph nodes in 26.3%, and lung in 25.6%. For patients for which the ECOG status was available (54.4%): 79.3% have an ECOG score between 0 and 1, 20.7% ≥2. Half the patients (48.8%) had only one metastatic site. CTX was given every three weeks to 2 patients (1.3%), every two weeks to 113 of patients (70.6%), and weekly to 45 (28.1%). For those receiving CTX every two weeks: 64.9% had irinotecan-based regimens (vs. 45.5% of those receiving CTX weekly, p=0.03), 31.5% had oxaliplatin-based regimens (vs. 47.7%, p=0.06), median duration of CTX use was 3.8 months (vs. 5.3 months, p=0.69) and that of 1st-line therapy 6.3 months (vs. 7.5 months, p=0.97), 69.0% discontinued 1st-line treatment (vs. 82.2%, p=0.09) - mainly for progression (71.8 vs. 75.7%, p=0.66) or toxicity (20.5 vs. 10.8%, p=0.20). Overall response evaluated for 100 patients receiving CTX every two weeks out of 113 was 46.0% (vs. 52.6%, p=0.49, evaluated for 38 receiving CTX weekly). CONCLUSIONS CTX administration every two weeks was the most frequent regimen. In this preliminary analysis, patients receiving weekly or every two weeks regimens had similar duration of treatment and response rate.

NSAIDs discontinuation and myocardial infarction.

In a recent letter, Garcia Rodriguez LA et al. [1] provide additional information on the risk of acute myocardial infarction (AMI) after discontinuing non-steroidal anti-inflammatory drugs (NSAIDs). The data were retrieved from THIN, a database of primary care records in the United Kingdom [2]. Among patients who had previously used NSAIDs for more than 1 year, the authors found that the risk of AMI remained increased during 3 (relative risk, RR, 1.74; 95% CI, 1.34–2.26) or 6 (RR, 1.61; 95% CI, 0.94–2.76) months after discontinuation, but returned to background risk thereafter (RR, 1.07; 95% CI, 0.64–1.81). They hypothesize a structural effect of long-term use of NSAIDs on the arterial wall or the genesis of arteriosclerosis, which would take at least 6 months to revert. We would like to offer a more mundane alternate explanation, that of persistent exposure to NSAIDs. Many pharmacoepidemiological studies use prescription data as a surrogate to assess drug exposure. It allows estimation of exposure to drugs when there is no possibility to confirm the patient s real drug intake. Though this is most likely appropriate for chronically and regularly used drugs such as antihypertensives or antidiabetic drugs [3,4], it has been shown that prescription or even drug delivery data from reimbursement databases were not really trustworthy to measure exposure for drugs with intermittent, symptomdriven use such as NSAIDs [3,5]. The fact that the persisting increased risk reported by Garcia Rodriguez LA et al. appeared mainly for long-term use (i.e. more than 1 year) could be explained by an unrecognized persistent use of NSAIDs after the end of the prescription period. This could occur through self-medication using the stockpiled prescribed NSAIDs, medication purchased OTC [6] or even that prescribed to other people [7]. French data have shown that for osteoarthritis, the main indication for long-term exposure toNSAIDs, the average reallife use is only about one-third of the daily defined dose used for the assessment of prescriptionor delivery-based exposure [5]. This could be particularly important, as Garcia Rodriguez LA et al. did not explicitly define continuous use. In absence of this definition, it is possible to imagine an unrecognized prolonged NSAID exposure after the end of prescription coverage because of intermittent self-treatment with leftover drugs [6]. This eventuality has previously been used by McDonald et al. [6] to justify an unexplainable persistent risk of gastrointestinal bleeding after 1 year from cessation of apparent exposure to NSAIDs. It is also hard to imagine in clinical practise that a patient who continuously took an NSAID for 1 year or more would completely stop using it for the next 6 months, unless this hypothetical patient underwent a surgical replacement of the hip or the knee. It would be consequently interesting to know the most frequent indications for NSAIDs in the THIN study, in particular for those patients in which myocardial infarction occurred after treatment withdrawal. In any case, exposure to NSAIDs may also persist through OTC medication that is ignored in both primary care and claims databases [3,5,6] and constitutes a particular issue in studies focusing on NSAIDs [8,9]. A European survey has shown that about onethird of patients in the United Kingdom affected by chronic pain had used OTC medication in the preceding 6 months, of which 47–63% were NSAIDs [10]. Furthermore, it could be simple to ask for and receive from neighbours, relatives or friends an NSAID painkiller for immediate use [7]. As a consequence, regardless of their legal status, the most popular self-administered substances were ibuprofen, diclofenac and piroxicam [7]. In conclusion, even if a long-term vascular effect of NSAIDs might be an explanation for the persistence of a cardiovascular risk during 6 months after cessation of prescription, actual cessation of intake should be proven first. In absence of this verification, one might also support the hypothesis of an increased immediate thrombotic risk related to the thromboxane/prostacycline imbalance induced by the COX-2 inhibition, or to the different endothelial/platelet induced by COX-1 inhibition, as proposed by the same authors in other papers [2,11]. Correspondence: Francesco Salvo, Université de Bordeaux, Inserm U 657, Bordeaux, France. Tel.: +33 630381308; fax: + 33 557574671. E-mail: fsalvo@unime.it